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Eur J Med Chem. 2017 Jan 5;125:1098-1106. doi: 10.1016/j.ejmech.2016.10.051. Epub 2016 Oct 24.

Design, synthesis, and biological evaluation of novel alkylsulfanyl-1,2,4-triazoles as cis-restricted combretastatin A-4 analogues.

Author information

1
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
2
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: youww@smu.edu.cn.
3
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: plzhao@smu.edu.cn.

Abstract

Thirty-two novel 3-alkylsulfanyl-1,2,4-triazole derivatives, designed as cis-restricted combretastatin A-4 analogues, were synthesized and evaluated for their antiproliferative activities. The results indicated that analogue 20 showed more potent antiproliferative activities against PC-3 cell lines than positive control CA-4. Particularly, the most promising compound 25 displayed 5-fold improvement compared to CA-4 in inhibiting HCT116 cell proliferation with IC50 values of 1.15 μM. Further flow-activated cell sorting analysis revealed that compound 20 displayed a significant effect on G2/M cell-cycle arrest in a dose-dependent manner in PC-3 cells. From this study, analogues 20 and 25 were the most potent anti-cancer agents in this structural class, and were considered lead compounds for further development as anti-cancer drugs.

KEYWORDS:

Alkylsulfanyl-1,2,4-triazoles; Antiproliferative activity; Synthesis

PMID:
27810596
DOI:
10.1016/j.ejmech.2016.10.051
[Indexed for MEDLINE]

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